Risk factors of epilepsy in children with complex febrile seizures: A retrospective cohort study.

BACKGROUND: Febrile seizures are the most common seizures in children. Children with complex febrile seizures have a higher risk of subsequent epilepsy compared with children with simple febrile seizures. Multiple risks factors for epilepsy, including focal status epilepticus, family history of epilepsy, neurodevelopmental abnormalities and abnormal electroencephalogram findings, have been found with inconsistent results. The aim of this study is to identify risk factors for developing epilepsy in children with complex febrile seizures. METHODS: The study included 248 children aged 3-72-months, diagnosed with complex febrile seizures at Chiang Mai University Hospital. Demographic data, seizure characteristics, electroencephalogram and neuroimaging findings were identified, and assessed to establish whether they were risk factors for subsequent epilepsy. RESULTS: Fifty-five patients (22.1%) had subsequent epilepsy. Using Cox regression-survival analysis, factors associated with epilepsy were prolonged seizures >15 min (P = 0.006; Hazard Ratio (HR): 2.475; 95% Confidence Interval (CI): 1.294-4.735), developmental delay (P = 0.019; HR: 4.476; 95% CI: 2.280-15.646), epileptiform discharges on electroencephalogram (P = 0.023; HR: 1.391; 95%CI: 1.174-1.876), and abnormal neuroimaging (computed tomography or magnetic resonance imaging; P = 0.028; HR: 1.355; 95% CI: 1.034-1.776). Age at onset, peak febrile temperature, duration between the onset of fever and the occurrence of seizure, recurrent seizures within 24 h, focal seizures, abnormal neurological exams and family history of febrile seizure or epilepsy were not associated with increased risk of subsequent epilepsy in this study. CONCLUSIONS: Risk factors associated with increased risk of epilepsy in children with complex febrile seizures are prolonged seizures or febrile status epilepticus, developmental delay, electroencephalogram epileptiform discharges, and abnormal neuroimaging. Their presence would merit close clinical monitoring.

Comparison of Arterial Ischemic and Hemorrhagic Pediatric Stroke in Etiology, Risk Factors, Clinical Manifestations, and Prognosis.

BACKGROUND: Stroke is relatively rare in children but has a significant impact on long-term morbidity and mortality. There are limited data regarding the etiology, clinical manifestation, and prognosis of arterial ischemic stroke (AIS) and hemorrhagic stroke (HS) in children. OBJECTIVE: The aim of this study is to identify and compare etiology, risk factors, clinical manifestations, and prognostic outcomes between arterial ischemic and hemorrhagic pediatric stroke. METHODS: We retrospectively reviewed all hospital medical records and pediatric neurology database of 83 children who were first diagnosed with AIS and HS at the Pediatric Department, Chiang Mai University Hospital, Chiang Mai, Thailand between January 1, 2009, and December 31, 2018. All children were from 1 month to 18 years old. RESULTS: Fifty-one AIS (56%) and 32 (35.2%) HS were identified. The median age of onset was 6.9 years for AIS and 5.3 years for HS. Moyamoya disease/syndrome was the most common cause in AIS (21.6%). Rupture of cerebral arteriovenous malformation was the most common cause in HS (21.9%). More than one-third (39%) of children had multiple risk factors associated with stroke. Iron deficiency anemia was commonly found in children with AIS (39.2%). The majority of clinical presentations were hemiparesis (80.4%) for AIS and alteration of consciousness (68.8%) for HS. The median time to diagnosis exceeded 6 hours in both AIS and HS. The overall mortality rate of acute stroke was 5.1 per 100 person-years (95% confidence interval [CI], 2.9-9). The mortality rate was higher in HS compared with that in AIS with statistical significance (16.6; 95% CI, 8.9-30.8 vs 1.1%; 95% CI, 0.3-4.6 per 100 person-years). Thirty children (36.1%) developed epilepsy during the follow-up (median duration, 26 months). Recurrent stroke occurred in 1 child with AIS and 1 child with HS. CONCLUSIONS: Moyamoya disease/syndrome and arteriovenous malformation rapture are the most common cause of AIS and HS, respectively. Iron deficiency anemia was commonly found in childhood AIS. The time to diagnosis in both AIS and HS was delayed. The mortality rate in HS was higher than in AIS. Neurological deficits are seen in 70% of childhood AIS during the follow-up. One-third of the children in our study developed epilepsy, which generally responds to a single antiseizure medication. The recurrence rate of childhood stroke was low compared with adult stroke.

Electrical status epilepticus in sleep (ESES) - Treatment pattern and EEG outcome in children with very high spike-wave index.

OBJECTIVE: The objective of the study was to determine electrical status epilepticus in sleep (ESES) outcome in children with very high spike-wave index (SWI; ≥85%), and assess treatment pattern. METHODS: Medical records of children 1-17 years old with ESES were reviewed. In this study, ESES is defined as SWI in non-rapid eye movement (non-REM) sleep of ≥85%. Electrical status epilepticus in sleep resolution is defined as reduction of SWI to <50%. RESULTS: Complete data were available in 33 children. Age at ESES diagnosis ranged from 32 to 165 months, median 76 months. The median duration of follow-up was 33 months. Two-thirds of the children were on one or more antiepileptic drugs (AED) at ESES diagnosis. Antiepileptic drugs were used as first treatment for ESES in 24/33 (73%). Electrical status epilepticus in sleep initially resolved in 76%, but 56% had subsequent relapse. The relapse rate was higher for steroids (89%) and benzodiazepines (60%) as compared with nonbenzodiazepine AEDs (29%). At last follow-up, ESES resolved in 21 children (64%). Electrical status epilepticus in sleep resolution was associated with seizure freedom (Fisher's exact, p < 0.05). SIGNIFICANCE: Using electroencephalogram (EEG) criteria, ESES resolved in 64%. We found high failure rate of first-line AEDs in preventing ESES, and high relapse rate. Standardization of ESES management is urgently needed.

The utility of EEG monitoring in neonates with hyperammonemia due to inborn errors of metabolism.

BACKGROUND: Continuous EEG studies demonstrate that neonates with seizures due to cerebral pathology, such as hypoxia ischemia, exhibit predominantly electrographic seizures (i.e. those only detected with EEG because they lack clinical features). Previous small case series demonstrate EEG changes and seizures during hyperammonemia associated with inborn errors of metabolism (IEM) but there are no reports utilizing continuous EEG in these conditions. OBJECTIVE: To characterize seizures and evaluate the utility of continuous EEG recording during hyperammonemia due to inborn errors of metabolism. METHODS: We retrospectively reviewed medical records and EEG tracings of neonates who presented with hyperammonemia due to inborn errors of metabolism who had continuous EEG and full medical records available for review, including follow up. RESULTS: Eight neonates with hyperammonemia were studied, 7 had urea cycle defects: Argininosuccinate lyase deficiency [3], (ornithine transcarbamylase deficiency [3], carbomyl phosphate synthase deficiency [1] and one had an organic acidemia: Methylmalonic acidemia [1]. Most common presentations were lethargy and poor feeding at 12-72 h of life. The highest blood ammonia level was 874 µmol/L (median); range 823-1647 µmol/L (normal value <50 µmol/L in term neonates). Seven were treated with hemodialysis in addition to nitrogen scavengers. Seven neonates had seizures; six had only electrographic seizures. Seizures initially occurred within 24-36 h of clinical presentation, sometimes with normal ammonia and glutamine levels. Neonates with seizures all lacked state changes on EEG. Inter burst interval duration correlated with degree of hyperammonemia. Two cases with normal plasma ammonia but increasing interburst interval duration were proven to have stroke by MRI. CONCLUSIONS: Seizures occur frequently in neonates with hyperammonemia; most can be detected only with continuous EEG. Seizures may occur when ammonia and glutamine levels are normal. Interburst interval duration is associated with ammonia levels or cerebral dysfunction from other brain pathology. Continuous EEG can be a useful tool for managing infants with hyperammonemia and may be essential for seizure management especially for infants in deep metabolic coma.

Pericardial effusion and cardiac tamponade after ventriculoperitoneal shunt placement: a case report.

Insertion of a ventriculoperitoneal shunt is a common neurosurgical procedure in both adult and paediatric patients. It is one of the most important treatments in cases of hydrocephalus; however, there is a wide range of complications: the most common complication being a shunt infection, and examples of rare complications are shunt migrations and cardiac tamponade. Several reports of distal ventriculoperitoneal shunt migration in different sites, including chest, right ventricle, pulmonary artery, bowel and scrotum were published. But pericardial effusion with cardiac tamponade and its relationship to distal ventriculoperitoneal shunt migration into the pericardial sac has never been reported.

Diagnostic Values of Red Flags and a Clinical Prediction Score for Emergent Intracranial Lesions in Non-Traumatic Pediatric Headaches.

INTRODUCTION: Diagnosis of emergent intracranial lesions that require emergency treatment either medically or surgically in non-traumatic pediatric headaches is important. Red-flag signs and symptoms are commonly used as justification for neuroimaging; however, evidence on its diagnostic values is limited. The study aims to identify diagnostic values of red-flags and develop a clinical prediction score to help improve the diagnostic yield of neuroimaging. METHODS: A retrospective review of 109 pediatric patients from 2006 to 2020 who presented with a non-traumatic headache was conducted. A clinical prediction score from red flags was developed using multivariate logistic regression. Discriminatory ability was examined using the area under the receiver operating characteristic curve. RESULTS: A total of 51 patients were diagnosed with emergent intracranial lesions. Four potential clinical red flag predictors were identified: (1) acute onset (less than 3 months), (2) altered conscious state, (3) focal motor abnormality, and (4) and ocular/pupillary abnormality or squint. A clinical prediction score was developed with good discriminatory properties (0.84). CONCLUSIONS: Clinical predictor scores from these four red flags may play an important role in maximizing neuroimaging and proper management for pediatric patients with non-traumatic headaches. Future validation studies are needed and could guide referrals and optimize the use of neuroimaging for these patients.

Short-term outcome of perinatal hypoxic-ischaemic encephalopathy at Chiang Mai University Hospital, Thailand: a 15-year retrospective study.

BACKGROUND: The outcome of perinatal hypoxic-ischaemic encephalopathy (HIE) in middle-to-low-income countries varies between regions. OBJECTIVES: To determine the mortality and morbidity, and factors influencing the deaths of infants with perinatal HIE. METHODS: A retrospective study was conducted at Chiang Mai University Hospital, Thailand. Perinatal HIE infants of >35 weeks gestation, birthweight ≥2000 g and admitted during 2005-2019 were reviewed. Baseline Characteristics, clinical course and outcome at discharge were compared between the period before and after initiation of therapeutic hypothermia (TH). Risk of death in HIE infants who underwent TH was identified. RESULTS: A total of 162 HIE infants were included. Compared to the period before TH initiation, the mortality rate was significantly decreased in the TH period. (27% vs. 12.8%, p=0.04) Among 100 HIE infants who underwent TH, the mortality rates was 14%(14/100), of whom 2.5% (2/76) and 50% (12/24) were in the moderate and severe HIE groups. Apgar score at 5 mins ≤1, severe HIE, seizures, hypoglycaemia, organ involvement ≥ five sites, ammonia ≥100 umol/L, lactate ≥14 mmol/L, and requirement for two or more inotropic drugs were risks of death. Multivariate analysis demonstrated that severe HIE (aOR 732.8, 95% CI 4.7-114643, p=0.01) and a need for two or more inotropic drugs (aOR 45.7, 95% CI 1.5-1040, p=0.029) were significant factors for mortality. CONCLUSION: In the period of TH, perinatal HIE infants had decreased mortality. Severe HIE and a need for two or more inotropic drugs were associated with death in the infant with HIE who underwent TH.Abbreviations: AED: anti-epileptic drug; BW, birthweight; CI: confidence interval; CMU: Chiang Mai University; EEG: electro-encephalogram; GA: gestational age; HIE: hypoxic-ischaemic encephalopathy; IQR: interquartile range; NICU: neonatal intensive care unit; SD: standard deviation; TH: therapeutic hypothermia.

Prenatal organophosphate exposure can cause adverse birth outcomes to humans.

Organophosphate (OP) pesticides may accumulate in pregnant agricultural workers, resulting in adverse effects on the growth and development of the fetus and neonates. This study aims to evaluate a possible association between prenatal urinary OP metabolite levels among pregnant agricultural workers and birth outcomes of infants. This study also investigated the factors associated with urinary OP metabolites among pregnant agricultural workers. The spot urine samples were collected and analyzed for six OP metabolite levels. Birth outcomes data were abstracted from medical records. Multiple regression analysis found that gestational age at childbirth was negatively associated with diethylphosphate (DEP) levels (ß = -0.073; 95% CI, -0.121, -0.024). Apgar score at 1 and 5 min after birth were negatively associated with diethyldithiophosphate (DEDTP) levels (ß = -0.036; 95% CI, -0.069, -0.003; and ß = -0.034, 95% CI, -0.057, -0.011, respectively). In addition, DEDTP levels were negatively associated with maternal age (ß = -0.181; 95% CI, -0.339, -0.023), and dimethylphosphate (DMP) levels were positively associated with frequency of agricultural work during pregnancy (ß = 31.554; 95% CI, 0.194, 62.914). Our results indicate that prenatal OP exposure can cause adverse birth outcomes in babies. Therefore, it is necessary to develop an effective strategy for reducing prenatal exposure to OP pesticides.

Organophosphate Pesticide Exposures in Early and Late Pregnancy Influence Different Aspects of Infant Developmental Performance

Organophosphate (OP) pesticides can transfer from mother to fetus via the placenta and amniotic fluid and may affect the development of infants. This study aims to evaluate the associations between maternal OP concentrations collected in the 1st-2nd trimester and the 3rd trimester of pregnancy and the infant developmental performance. The Screening Test of the Bayley Scales of Infants and Toddler Development, Third Edition (BSID-III screening test) was used to assess development performance at 2 and 6 months of age. Multiple regression analysis showed a negative correlation between cognitive performance at 2 months and maternal diethylthiophosphate (DETP) levels in the 1st-2nd trimester (ß ± SE = -0.012 ± 0.004, p < 0.05). We also found that expressive communication and fine motor performance at 6 months were negatively associated with maternal diethyldithiophosphate (DEDTP) levels in the 3rd trimester (ß ± SE = -0.047 ± 0.016, p < 0.05, and ß ± SE = -0.044 ± 0.017, p < 0.05, respectively). These results suggest that maternal ethylated OP concentrations at different timing of exposure during pregnancy may influence different aspects of infant developmental performance.

Spatiotemporal distribution and age of seizure onset in a pediatric epilepsy surgery cohort with cortical dysplasia.

OBJECTIVE: Focal Cortical Dysplasias (CD) are a common etiology of refractory pediatric epilepsy and are amenable to epilepsy surgery. We investigated the association of lesion volume and location to age of seizure onset among children with CD who underwent epilepsy surgery. METHODS: A retrospective study of epilepsy surgery patients with pathologically-confirmed CD. Regions of interest (ROI) determined preoperative lesion volumes on 1.5 T and 3 T T2 and SPGR MRIs, and location in 7 distributed neural networks. Descriptive and inferential statistics were used. RESULTS: Fifty-five patients were identified: 35 girls (56.5 %). Median age of seizure onset: 19.0 months (range 0.02 months - 16.0 years). Median age of surgery: 7.8 years (range 2.89 months - 24.45 years). CD were frontal (n = 21, 38 %); temporal (n = 15, 27 %); parietal (n = 10, 18 %); occipital (n = 3, 5%); multilobar (n = 6, 11 %). Frontal FCD had seizure onset < 1-year-old (P = 0.10); temporal lobe CD seizure onset was more likely > 5-years-old (P= 0.06). Median lesion volume for CD was 23.23 cm3 (range: 1.87-591.73 cm3). Larger CD lesions were associated with earlier epilepsy (P = 0.01, r = -0.16). We did not find that lesions proximal to early maturing cortical regions were associated with earlier seizure onset. We found an association with CD location in the default mode network (DMN) and age onset < 5years old (P = 0.03). Age of seizure onset was negatively correlated with percent of CD overlapping motor cortex (P = 0.001, r =-0.794) but not with CD overlap of the visual cortex (P = 0.35). There was no effect of CD type on age of epilepsy onset. SIGNIFICANCE: Larger CD lesions are associated with earlier onset epilepsy. CD most commonly occurs within the DMN and Limbic network, and DMN is associated with seizure onset before 5-years-old. Percent of CD overlapping motor cortex correlates with earlier seizure onset. These observations may reflect patterns of brain maturation or regional differences in clinical expression of seizures.

Incidence and Geographic Distribution of Succinic Semialdehyde Dehydrogenase (SSADH) Deficiency.

The incidence of succinic semialdehyde dehydrogenase (SSADH) deficiency, an autosomal recessive inherited disorder of GABA degradation, is unknown. Upon a recent diagnosis of a new family of affected fraternal twins from the Punjabi ethnic group of India, case ascertainment from the literature and our database was done to determine the number of confirmed cases along with their geographic distribution. The probands presented with global developmental delay, infantile onset epilepsy, and a persistent neurodevelopmental disorder upon diagnosis at 10 years of age with intellectual disability, expressive aphasia, and behavioral problems most prominent for hyperactivity. Gamma-hydroxybutyric aciduria and homozygous ALDH5A1 c.608C>T; p.Pro203Leu mutations were confirmed. Identification of all available individual cases with clinical details available including geographic or ethnic origin revealed 182 patients from 40 countries, with the largest number of patients reported from the USA (24%), Turkey (10%), China (7%), Saudi Arabia (6%), and Germany (5%). This study provides an accounting of all published cases of confirmed SSADH deficiency and provides data useful in planning further studies of this rare inborn error of metabolism.

Intravenous levetiracetam in Thai children and adolescents with status epilepticus and acute repetitive seizures.

BACKGROUND: Intravenous levetiracetam is an option for treatment of status epilepticus (SE) and acute repetitive seizures (ARS). However, there have been relatively few studies with children and adolescents. Also, an appropriate dosage has yet to be determined. AIM: This study investigated the safety and the efficacy of levetiracetam for intravenous treatment of convulsive status epilepticus and acute repetitive seizures in children and adolescents. METHOD: Retrospectively, the study reviewed the medical records of 19 male and 31 female patients under 18 years of age who had received intravenous levetiracetam treatment either for acute repetitive seizures or for convulsive status epilepticus. The patients were admitted between April 1st, 2010 and December 31st, 2011 to the Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. Data were collected on underlying illnesses, etiology of seizures, indication for levetiracetam therapy, initial dosage, rate of infusion, untoward effects during infusion and emerged complications. Efficacy of treatment was defined as the termination of seizure within 30 min of completing levetiracetam infusion and no seizure recurrence within 6 h of initial treatment. RESULTS: The age range of the 50 patients was from one day to 18 years (mean 79.6 months). The analysis included 52 episodes of 34 acute repetitive seizures (63.4%) and 18 convulsive status epilepticus (34.6%). Infusion rates ranged from 2 to 66 mg/kg/min (mean 29.6). Cessation of seizure was obtained in 59.6% of 52 episodes. Patients with underlying drug resistant epilepsy did not respond to levetiracetam therapy as well as patients with other etiology of seizures. There were no adverse drug reactions or untoward effects observed during the therapy. CONCLUSION: Intravenous administration of levetiracetam is safe and effective for treatment of acute repetitive seizures and convulsive status epilepticus in children and adolescents. Failure of treatment may be related to underlying drug resistant epilepsy. Further study of appropriate initial dosage and pharmacokinetic variations in the patients is needed as possible explanation of the unresponsiveness.